Phorbol myristate acetate (PMA) and other tumor promoting substances will be examined for both their potential for lymphocyte mitogenesis and their ability to displace 3HPMA in binding studies on whole cells. In addition we will study the biology of the normal lymphocytes' response to PMA, specifically the binding of PMA to whole cells, to "purified" populations of "B" and "T" cells and "glass" adherent cells (which will also include some B and T cells), to cells treated with steroids and by preincubation. We will also examine the long-term binding of PMA to the lymphocyte and in initial ways its metabolism. These studies should give us some insight as to the relationship of binding to eventual mitogenesis. We may be able to recognize a group of cells which bind PMA within a certain range of number of molecules. We will get other specific information on the possible loss of responsivenes due to loss of receptors, the endocytosis of PMA as well as a picture of binding after prior stimulation with nonradioactive PMA in long-term studies. In addition to the binding studies above the biology of PMA interaction with different "pure" cell populations and their recombination should reveal some of the basic interactions that take place in the unpurified system. It is expected that these studies should reveal a portion of the biological mode of action of a cocarcinogen in a normal cell population as well as some of the ways in which these normal cells interact with each other.